A5057652778- Inflammatory Bowel Disease
- Growth Hormone and Insulin-like Growth Factors
- TGF-β signaling in diseases
- Gastrointestinal motility and disorders
- Microscopic Colitis
- Eosinophilic Esophagitis
- Helicobacter pylori-related gastroenterology studies
- Metabolism, Diabetes, and Cancer
- Pancreatitis Pathology and Treatment
- Autoimmune and Inflammatory Disorders
- Protein Tyrosine Phosphatases
- Ion channel regulation and function
- Genetic factors in colorectal cancer
- Cell Adhesion Molecules Research
- Digestive system and related health
- Ion Channels and Receptors
- PI3K/AKT/mTOR signaling in cancer
- Pancreatic and Hepatic Oncology Research
- Gastroesophageal reflux and treatments
- Neuropeptides and Animal Physiology
- Medical and Biological Ozone Research
- Nitric Oxide and Endothelin Effects
- Cytokine Signaling Pathways and Interactions
- Gastrointestinal Tumor Research and Treatment
- Cancer, Hypoxia, and Metabolism
Virginia Commonwealth University
2011-2021
Virginia Commonwealth University Medical Center
2005-2021
University Health System
2016-2017
Institute of Molecular Biology and Biophysics
2012-2014
Philadelphia University
2011
University of Aberdeen
2011
University of New Haven
2011
New York Proton Center
2011
Southwestern University
2011
University of Chicago
2011
KELLUM, JOHN M. M.D.; KUEMMERLE, F. O'DORISIO, THOMAS RAYFORD, PHILLIP Ph.D.; MARTIN, DANIEL ENGLE, KATHERINE R.N.; WOLF, LUKE M.A.; SUGERMAN, HARVEY J. M.D. Author Information
The intestinal peristaltic reflex can be elicited by mucosal stimulation or circular muscle stretch. Muscle stretch activates extrinsic, whereas intrinsic calcitonin gene-related peptide (CGRP)-containing sensory neurons. present study examined the role of 5-hydroxytryptamine (5-HT) in transmission. A three-compartment preparation rat colon was used that enables separate measurement transmitters and modulators. Mucosal stimuli (2-8 brush strokes) caused concurrent increase 5-HT CGRP release...
We have previously shown that agonist-induced Ca2+ mobilization in intestinal longitudinal muscle is mediated by ryanodine-sensitive, inositol 1,4,5-trisphosphate-insensitive sarcoplasmic channels. release via these channels triggered agonist-stimulated influx and results Ca2+-induced release. The present study examined whether cyclic ADP-ribose (cADPR) synthesized response to stimulation of agonists modulates the activity Cyclic ADPR bound with high affinity dispersed cells (IC50 1.9 nM)...
The aim of this study was to identify the nitric oxide synthase (NOS) isoform expressed in freshly dispersed rabbit gastric smooth muscle cells and cultured gastric, human intestinal, guinea pig taenia coli cells. RT-PCR products predicted size (354 bp) were obtained with endothelial NOS (eNOS)-specific primers, but not neuronal (nNOS)- or inducible (iNOS)-specific all preparations except coli. Control studies showed absence markers, platelet cell adhesion molecule-1 (PECAM-1) vascular...
Abstract Increased TGF-β1 and TGF-β1–dependent Collagen I production in intestinal mesenchymal cells result fibrosis patients with Montreal B2 fibrostenotic Crohn’s disease. Numerous cytokines, including IL-6, are produced by activated themselves activate STAT3. The aim of the current study was to determine mechanisms which STAT-3 activation might fibrosis. Cytokine levels were measured ELISA. STAT3 suppressor cytokine signaling 3 protein immunoblot, STAT3-TGFB1 DNA–binding activity...
The actin cytoskeleton is a critical regulator of intestinal mucosal barrier permeability, and the integrity epithelial adherens junctions (AJ) tight (TJ). Non muscle myosin II (NM II) key cytoskeletal motor that controls filament architecture dynamics. While NM has been implicated in regulation vitro, little known about its roles mucosa vivo. In this study, we generated mouse model with an epithelial-specific knockout IIA heavy chain cKO) examined structure function normal gut barrier,...
BackgroundStrictures develop in >30% of patients affected with Crohn's disease. No available medication prevents stricture development susceptible patients. In strictures, but not adjacent normal intestine, TGF-β1 increases muscularis smooth muscle, increasing collagen I production and strictures. Muscle cells express αVβ3 integrin containing an Arg-Gly-Asp (RGD) binding domain. The aim was to determine whether increased levels strictures were the result latent TGF-β1, which contains RGD...
Whether or not populations diverge with respect to the genetic contribution risk of specific complex diseases is relevant understanding evolution susceptibility and origins health disparities. Here, we describe a large-scale whole-genome sequencing study inflammatory bowel disease encompassing 1,774 affected individuals 1,644 healthy control Americans African ancestry (African Americans). Although no new loci for are discovered at genome-wide significance levels, identify numerous instances...
Endogenous insulin-like growth factor-1 (IGF-I) stimulates of cultured human intestinal smooth muscle by activating distinct mitogen-activated protein (MAP) kinase-dependent and phosphatidylinositol 3-kinase-dependent signaling pathways. In Rat1 Balb/c3T3 fibroblasts in neurons the IGF-I receptor is coupled to an inhibitory G protein, Gi, which mediates Gβγ-dependent MAP kinase activation. The present study determined whether normal cells activates a heterotrimeric role activation mediating...
Intraluminal nutrients in the gut affect peristaltic reflex, although mechanism is not well defined. Recent evidence supports presence of taste receptors and their signaling components enteroendocrine cells, function unclear. This study aimed to determine if modify colonic motility through activation receptors. Colonic sections were immunostained for umami receptor T1R1/T1R3, which mediates response ligands, such as monosodium glutamate (MSG), cells. Ascending contraction, descending...
Abstract Background In humans, inflammation of either the urinary bladder or distal colon often results in sensory cross-sensitization between these organs. Limited information is known about mechanisms underlying this clinical syndrome. Studies with animal models have demonstrated that activation primary afferent pathways may a role mediating viscero-visceral cross-organ sensitization. Methods Colonic was induced by single dose tri-nitrobenzene sulfonic acid (TNBS) instilled...
Abstract Background Endoplasmic reticulum (ER) stress is an essential response of epithelial and immune cells to inflammation in Crohn’s disease. The presence mechanisms that might regulate the ER subepithelial myofibroblasts (SEMFs) its role development fibrosis patients with disease have not been examined. Methods Subepithelial were isolated from affected ileum normal each Montreal phenotype non-Crohn’s subjects. Binding GRP78 latent TGF-β1 subcellular trafficking was examined using...
Insulin-like growth factor-binding protein-5 (IGFBP-5) and insulin-like factor-I (IGF-I) are produced by human intestinal smooth muscle cells. Endogenous IGF-I stimulates increases IGFBP-5 secretion. augments the effects of facilitating interaction with receptor tyrosine kinase. Andress (Andress, D. L. (1998) <i>Am. J. Physiol.</i> 274, E744–E750) Berfield <i>et al.</i> (Berfield, A. K., Andress, L., Abrass, C. K. (2000) <i>Kidney Int.</i> 57, 1991–2003) have shown that in osteoblasts kidney...
The role of protein kinase C (PKC) in sustained contraction was examined intestinal circular and longitudinal muscle cells. Initial induced by agonists (CCK-8 neuromedin C) abolished 1) inhibitors Ca 2+ mobilization (neomycin dimethyleicosadienoic acid), 2) calmidazolium, 3) myosin light chain (MLC) (MLCK) inhibitor KT-5926. In contrast, not affected these but the PKC chelerythrine calphostin C, PKC-ε antibody, a pseudosubstrate inhibitor. GDPβS both initial contraction, whereas Gα q/11...
Transdifferentiation of epithelial cells into mesenchymal and myofibroblasts plays an important role in tumor progression tissue fibrosis. Such plasticity is accompanied by dramatic reorganizations the actin cytoskeleton, although mechanisms underlying cytoskeletal effects on transdifferentiation remain poorly understood. In present study, we observed that selective siRNA-mediated knockdown γ-cytoplasmic (γ-CYA), but not β-cytoplasmic actin, induced epithelial-to-myofibroblast transition...
Insulin-like growth factor I (IGF-I), acting via its cognate receptor, plays an autocrine role in the regulation of intestinal muscle cells. In present study signaling pathways mediating effects IGF-I were characterized cultured human smooth Growth induced by a maximally effective concentration (100 nM), measured as [ 3 H]thymidine incorporation, was only partially inhibited LY-294002 [phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor] or PD-98059 [mitogen-activated protein (MAP) kinase...